The present application relates to a method for preparing and isolating salts of 6-chloropurine with strong acids and to the novel salts prepared by the method.
Various methods for preparing 6-chloropurines are known in the art. W. A. Nasutavicus et al., J. Het. Chem., 11, 77(1974) disclose treating hypoxanthines with phosphorus pentasulfide to give the corresponding mercaptopurines and converting the latter to 6-chloropurines by chlorination with chlorine in hydrochloric acid or acetonitrile.
The chlorination of hypoxanthines with phosphorus oxychloride in the presence of N,N-dimethyl- or diethylaniline is well documented in the literature. Bendich, et al., J. Am. Chem. Soc., 76, 6073(1954) disclose the preparation of 6-chloropurine by the treatment of hypoxanthine with phosphorus oxychloride in the presence of N,N-dimethylaniline via continuous extraction with ether from an acidic aqueous solution, G. H. Hutchins et al have disclosed, in U.S. Pat. No. 2,746,961, that 6-chloropurine can be recovered from the chlorination mixture with methanol after removal of excess phosphorus oxychloride. The isolation of 6-chloropurine from acidic aqueous solution by toluene extraction (Japanese Pat. No. 6,918, 1967) and by salting out with salt (Beaman et al., J. Appl. Chem. 12, 432, 1962) have been reported.
The known methods for preparing 6-chloropurine are not entirely satisfactory because of the difficulties in isolating the product from the reaction mixture. The isolation of the product by continuous solvent extraction is a long and tedious process and is not convenient for large scale preparation of the compound.
The present application is directed to a method for preparing and isolating salts of 6-chloropurine with strong acids which can be converted conveniently to 6-chloropurine.